Researchers at HIPS Develop Innovative Model for Testing Drugs Against Hair Follicle Infections

3D-Printed Hair Follicle Model Could Revolutionize Infection Research and Reduce Animal Testing

Infections of the hair follicle are often difficult to treat because bacteria nestle in the narrow gap between the hair and skin, where drugs struggle to reach them. To study this scenario more effectively in the lab, researchers from the Drug Delivery Across Biological Barriers department at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) have developed a model in which human hair follicles are embedded in a 3D-printed matrix. This system will allow future testing of new drug candidates against such pathogens directly on human follicles. The team has now published its findings in the journal ACS Biomaterials Science & Engineering.

Hair follicles are complex structures that surround the hair root, anchoring it in the skin and providing stability. At the same time, the space between the skin and follicle offers microorganisms ideal conditions to multiply unchecked. This often leads to chronic follicle inflammation, which is not only painful but, in cases of acne inversa (hidradenitis suppurativa), can also trigger secondary diseases such as diabetes mellitus or even acute sepsis. In Germany alone, approximately 830,000 people currently suffer from this condition.

To successfully develop new drugs for hair follicle infections, lab models that realistically replicate the physiological conditions of the skin are essential. A team led by Prof. Claus-Michael Lehr at HIPS—a site of the Helmholtz Centre for Infection Research (HZI) in collaboration with Saarland University—has now created such a model. By transplanting living human hair follicles into a collagen matrix within a 3D-printed polymer scaffold, the researchers successfully mimicked the natural environment of the follicles. "This model has the advantage of allowing us to test new drug candidates in the follicle microenvironment at an early stage of development without relying on animal experiments," says Samy Aliyazdi, the study's lead author.

Previously, new drug candidates for hair follicle infections were first tested using simpler models, such as free-floating human follicles in liquid culture. However, these models inadequately reflect real conditions in patients and are therefore not ideal for biological efficacy studies. Using the new 3D model, the researchers have already demonstrated that nanoparticles achieve better penetration and distribution within hair follicles compared to free-floating cultures. Nanoparticles are thus capable of deeply infiltrating follicles and serve as effective drug carriers. Additionally, Lehr's team showed that infections caused by the hospital-acquired bacterium Staphylococcus aureus can be combated far more effectively when the antibiotic rifampicin is first encapsulated in such nanoparticles.

The newly developed 3D model of human hair follicles addresses several limitations of previous lab systems. "Our model provides a more realistic replication of the human follicle microenvironment and can be cultivated long-term," says Aliyazdi. "But we're not done yet: further optimizations are needed, particularly regarding the mechanical properties of the polymer. We also plan to incorporate additional cell types, such as fibroblasts and immune cells, to make the model even more representative of the conditions in patients." A more complex model of this kind holds great potential for gaining early insights into follicle viability, pathogen behavior, and, ultimately, the predictability of drug efficacy and safety assessments. Lehr emphasizes: "Our research shows that replicating the natural follicle environment is crucial for evaluating antibiotic effectiveness. This model could significantly accelerate the development of new, targeted therapies while reducing the need for animal testing."